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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-05-1408. This Article Full Text (PDF) All Versions of this Article: 2003-05-1408v1 102/10/3668    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuppner, M. C Articles by Issels, R. D Search for Related Content PubMed PubMed Citation Articles by Kuppner, M. C Articles by Issels, R. D Social Bookmarking                   What's this? Submitted May 5, 2003 Accepted June 29, 2003 Ifosfamide impairs the allostimulatory capacity of human dendritic cells by intracellular glutathione depletion Maria C Kuppner*, Anabel Scharner, Valeria Milani, Christoph von Hesler, Katharina E Tschoep, Oksana Heinz, and Rolf D Issels Klinikum Grosshadern Medical Clinic III, Ludwig-Maximilians-University of Munich, Munich, Germany National Research Center for Environment and Health, Institute of Molecular Immunology, Munich, Germany Clinical Cooperation Group on Hypthermia, Ludwig-Maximilians-University Munich, Munich, Germany * Corresponding author; email: kuppner{at}gsf.de. Ifosfamide a clinically potent chemotherapeutic agent causes depletion of intracellular glutathione (GSH) levels in different cell types. GSH is the major intracellular reductant against oxidative stress. 4-hydroxyifosfamide (4-OH-IF), the activated form of ifosfamide, depletes GSH levels in T cells and NK cells which is accompanied by a decrease in T cell and NK function. Here we demonstrate for the first time that human monocyte derived dendritic cells (DC) express higher constitutive levels of GSH and are less sensitive to 4-OH-IF induced GSH depletion in comparison to T cells and NK cells. Treatment of DC with 4-OH-IF significantly reduced their ability to stimulate allogeneic T cell proliferation and IFN production. Ifosfamide also decreased DC IL-12p70 production after stimulation with LPS and IFN. The decrease in allostimulatory capacity and in IFN and IL-12 production correlated with a decrease in intracellular GSH in the DC. The responses could be restored by reconstituting DC GSH levels with glutathione monoethyl ester (GSH-OEt). 4-OH-IF had no inhibitory effect on the ability of DC to present exogenously added tyrosinase peptide to tyrosinase specific CTL. These studies suggest that in cancer patients treated with ifosfamide protection strategies based on glutathione reconstitution may enhance DC function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. Williams, T. Rangasamy, S. M. Bauer, S. Killedar, M. Karp, T. W. Kensler, M. Yamamoto, P. Breysse, S. Biswal, and S. N. Georas Disruption of the Transcription Factor Nrf2 Promotes Pro-Oxidative Dendritic Cells That Stimulate Th2-Like Immunoresponsiveness upon Activation by Ambient Particulate Matter J. Immunol., October 1, 2008; 181(7): 4545 - 4559. [Abstract] [Full Text] [PDF] A. Agrawal, P. Kaushal, S. Agrawal, S. Gollapudi, and S. Gupta Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells J. Leukoc. Biol., February 1, 2007; 81(2): 474 - 482. [Abstract] [Full Text] [PDF] J. Zhang, M. A. Alston, H. Huang, and R. L. Rabin Human T cell cytokine responses are dependent on multidrug resistance protein-1 Int. Immunol., March 1, 2006; 18(3): 485 - 493. [Abstract] [Full Text] [PDF]

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